title: Structural and functional characterization of two alpha-synuclein strains.
abstract: α-Synuclein aggregation is implicated in a variety of diseases including Parkinson's disease, dementia with Lewy bodies, pure autonomic failure and multiple system atrophy. The association of protein aggregates made of a single protein with a variety of clinical phenotypes has been explained for prion diseases by the existence of different strains that propagate through the infection pathway. Here we structurally and functionally characterize two polymorphs of α-synuclein. We present evidence that the two forms indeed fulfil the molecular criteria to be identified as two strains of α-synuclein. Specifically, we show that the two strains have different structures, levels of toxicity, and in vitro and in vivo seeding and propagation properties. Such strain differences may account for differences in disease progression in different individuals/cell types and/or types of synucleinopathies.
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Bousset
authors.forename: Laura
authors.initials: L
authors.lastname: Pieri
authors.forename: Gemma
authors.initials: G
authors.lastname: Ruiz-Arlandis
authors.forename: Julia
authors.initials: J
authors.lastname: Gath
authors.forename: Poul Henning
authors.initials: PH
authors.lastname: Jensen
authors.forename: Birgit
authors.initials: B
authors.lastname: Habenstein
authors.forename: Karine
authors.initials: K
authors.lastname: Madiona
authors.forename: Vincent
authors.initials: V
authors.lastname: Olieric
authors.forename: Anja
authors.initials: A
authors.lastname: Böckmann
authors.forename: Beat H
authors.initials: BH
authors.lastname: Meier
authors.forename: Ronald
authors.initials: R
authors.lastname: Melki
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D017510:Protein Folding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D053838:Scattering, Small Angle; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology
chemical_list: D020033:Protein Isoforms; D011994:Recombinant Proteins; D051844:alpha-Synuclein